Polypeptides play an important role in today's medical portfolio. Expression systems for the production of recombinant polypeptides are well-known. For human application every pharmaceutical substance has to meet distinct criteria. To ensure the safety of biopharmaceutical agents to humans, for example, nucleic acids, viruses, and host cell proteins, which would cause severe harm, have to be removed. To meet the regulatory specification one or more purification steps have to follow the manufacturing process. Among other, purity, throughput, and yield play an important role in determining an appropriate purification process.
Due to their chemical and physical properties, such as molecular weight and domain architecture, including secondary modifications, the downstream processing of immunoglobulins is essential. For example, concentrated solutions are required not only for formulated drugs but also for intermediates in downstream processing (DSP) to achieve low volumes for economic handling and application storage. Furthermore, fast concentration processes are favored to ensure smooth processes and short operating times. In this context tangential flow filtration (TFF) processes are used.
Saxena, A., et al. report membrane-based techniques for the separation and purification of proteins (Adv. Colloid Interfacial Sci. 145 (2009) 1-22. In WO 2009/010269 a variable tangential flow filtration method is reported. Mignard, D., et al. report fouling during the cross-flow ultrafiltration of proteins (J. Membr. Sci. 186 (2001) 133-143). An optimization diagram for membrane separations is reported by Van Reis, R., et al., J. Membr. Sci. 129 (1997) 19-29).
Thermodynamic non-ideality of protein containing solutions during membrane based processes has been reported by Donnan, F. G., Z. Elektrochem. 17 (1911) 572-581. Stoner et al. (J. Pharm. Sci. 93 (2004) 2332-2342) reported the concentration of charged solutes encompassing chloride, histidine and acetate during dialysis of the different proteins at various protein concentrations.